Pancreatic cysts occur in more than 20% of patients evaluated at autopsy and in 2.4% to 13% of patients studied by abdominal imaging (CT scan or MRI) for reasons unrelated to pancreatic pathology (1-4). In view of the ever-increasing use of abdominal imaging and continuing improvements in the resolution of these technologies, the diagnosis of these lesions, often as incidental findings, can be expected to rise. They pose a challenging management problem because some cysts represent bona fide precursor lesions to invasive pancreatic ductal adenocarcinomas (PDAs), while others have minimal neoplastic potential (5). Yet, distinguishing cystic neoplasms from one another on the basis of clinical, imaging, and standard laboratory criteria is often not possible. Because of the diagnostic dilemmas posed by these lesions, and the potentially lethal consequences of an incorrect clinical diagnosis, some patients with harmless cysts are over-treated by surgical resection of the cyst and part of the pancreas (6). These pancreatectomies are major surgical procedures associated with significant morbidity and even rare mortality, prompting most investigators to adopt a watchful waiting approach with frequent imaging, sometimes employing endoscopic ultrasound (EUS) surveillance (7). New diagnostic modalities that will improve the management of the numerous patients with pancreatic cysts are therefore urgently needed.
There are three main types of pancreatic cystic neoplasms (8). Serous cystic adenomas (SCAs) account for ˜10% of surgically resected cystic lesions of the pancreas (8, 9). These cysts are thought to be totally benign with essentially no likelihood of becoming invasive (that is, of becoming PDA). Intraductal papillary mucinous neoplasms (IPMNs), representing ˜20% of surgically resected cystic lesions of the pancreas (8, 9), occur in either the main pancreatic duct and/or branch ducts. Those in the main ducts are most aggressive, as ˜45% are found to have progressed to invasive carcinoma at the time of surgical resection (10). Those in branch ducts are found to have progressed to invasive carcinoma in ˜20% of patients (10). IPMNs can also be classified into three histologic subtypes—intestinal, pancreatobiliary, and gastric—based on the resemblance of their epithelial cells to those of the corresponding normal tissues. The natural history of IPMNs, regardless of their histology or location within the pancreas, is not known with certainty because the lesions are often excised when they reach a certain size (3 cm diameter) or become symptomatic. However, based on the age of patients with resected lesions, there appears to be a 5-year lag time from non-invasive IPMN (average age 63.2 years) to invasive IPMN (average age 68.1 years) (11). The third type of pancreatic cystic neoplasms, representing 5 to 10% of surgically resected pancreatic cysts, are called Mucinous Cystic Neoplasms (MCNs) These progress to invasive carcinomas less often than IPMNs: only ˜10% of MCNs contain an invasive component when surgically excised (12). Moreover, MCNs are less diagnostically challenging because most lesions occur in the body or tail of the pancreas in relatively young women. The average age of women with MCNs is more than 20 years less than that of patients with either SCAs or IPMNs (12). The remainder of surgically resected cystic lesions of the pancreas are a heterogeneous group of retention cysts, congenital cysts, and other rarer lesions.
PDAs can be divided into two types: those that develop in the absence of cystic lesions and those that develop from a cystic lesion. The vast majority of PDAs that develop from cystic lesions do so from IPMNs, as SCAs do not give rise to PDAs and MCNs are less common than IPMNs. Interestingly, the prognoses of patients with PDAs developed from IPMNs are different from those in patients with PDAs that develops in the apparent absence of IPMNs (11, 13). The survival of patients with surgically resected PDAs associated with IPMNs is as high as 45% at 5 years (11, 13). In contrast, survival is very rare in other PDA patients (14). While some of the difference in survival is due to differences in stage at diagnosis, investigators have suggested that “carcinoma arising in IPMNs is a different disease” from the more common type of PDA that develops without any associated cystic precursor (15).
There is a continuing need in the art to develop tools for detecting and distinguishing different forms of cancer so that appropriate treatments may be administered and inappropriate treatments unlikely to be successful may be withheld.